Artemisia annua, known commonly as sweet wormwood, has been used medicinally since at least the 4th century CE, when Chinese physicians created a fever-reducing tea called qinqhao from the plant’s leaves. In the 1970s, during investigations of the plant’s medicinal properties, researchers isolated a substance called artemisinin from leaf extracts. The compound now is one of the most effective substances available for the treatment of severe malaria.

But A. annua farmers have struggled to produce enough plant material to supply global demand for artemisinin. And according to Ian A. Graham and Dianna Bowles, researchers at the University of York’s Centre for Novel Agricultural Products (CNAP), many A. annua plants currently grown for commercial purposes in places such as Africa and China are in fact suboptimal artemisinin producers. “Either good yielding varieties are not available, or the seed is too expensive for farmers to use,” the researchers explained.

Ian A. Graham and Dianna Bowles, leaders of the CNAP Artemisia Research Project.

In early 2010, Graham, Bowles, and colleagues reported the discovery of sites within the A. annua genome that control artemisinin production in the plant’s leaves. They are now using this information to develop lines of plants that produce high quantities of artemisinin, which would help ensure a steady supply of the drug and improve the livelihoods of Artemisia growers.

Artemisinin yields from cultivated plants vary greatly. “Yield depends on the quantity of leaves produced and the amount of artemisinin extracted from those leaves,” Graham and Bowles said. “This is influenced by plant variety, climate, soil pH, and plant nutrition. For example, wild-collected plants have low yields (less than 500 kg of dry matter per hectare and 0.03–0.3 percent artemisinin by weight). With good varieties, good conditions, and good management, plants can yield around 1.5 to 2 tons of dry matter per hectare and 0.5–1.2 percent artemisinin.”

To figure out what makes certain varieties of A. annua better artemisinin producers than others, the researchers created a genetic map of the plant, focusing in particular on the genetics of high artemisinin-yielding plants. “The map helps us to recognize young plants as potential high performers from their genetics, instead of having to grow them to maturity and seeing how they perform,” Graham and Bowles explained. “The map also helps to inform the selection of genetically distinct parent plants for breeding high-yielding hybrids.”

To create the map, however, the researchers first needed to sequence A. annua’s DNA. “We studied the genetic sequences associated with active genes, sequencing around 360 million base pairs,” they said. Using the sequence information, they were able to identify target genes, or genes they believed may exert some control over the plant’s ability to produce artemisinin. They then identified specific variations in the plant’s DNA that could serve as molecular indicators of artemisinin yield.

“The genetic variant can be used as a molecular marker for field performance,” Graham and Bowles explained. “To develop molecular markers, we grew populations of plants in the field and assessed them for their performance and genetics. A strong association between a genetic variant and an aspect of performance indicates that the two are often inherited together.”

The CNAP team also used the genetic maps to identify associations between genetic features indicative of high artemisinin production and physical characteristics of the plants. “The Artemisia plant makes and stores artemisinin only in the trichomes, which are found on the plant’s surface, mainly on the leaves. So increasing leaf area, trichome density, or plant weight will all lead to increased yields.”

The CNAP molecular plant-breeding approach could have a substantial impact on global A. annua cultivation and artemisinin production. “Molecular plant breeding reduces the number of generations it takes to produce the new varieties and enables promising plants to be selected at an earlier stage after each cross,” the researchers said. “We reckon it has probably about halved the time we’ll take to produce hybrid varieties.”

The molecular breeding methods developed by CNAP could be implemented very soon. The ability to grow high artemisinin-yielding plants could bring much needed decreases in production costs for A. annua farmers, the majority of whom live in impoverished regions.

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